Research Projects > Protein Structure-Function Relationships


The enzyme lactate dehydrogenase (LDH) is a key enzyme in high-performance glycolytic tissues such as fast-twitch muscle and solid tumor cells. In these tissues, high metabolic activity exceeds the aerobic capactiy and glycolysis produces ATP through fermentation, producing excess acid that causes intracellular pH to drop. This acidosis can be destablizing to enzymatic proteins, but in vivo metabolic enzymes may be protected through protein-protein interactions.

We are examining how changes in LDH primary structure, tertiary structure, and protein-interaction networks act to stabilize the enzyme and to regulate its activity. Our results suggest that LDH is in a metabolon complex in the cell that stabilizes and reduces catalytic activity in cell-free extracts (Cayenne et al 2011, Stillman and Somero 2001).

We have been able to induce LDH stabilization through intensive exercise (and perhaps physiological hypoxia) in porcelain crab species where LDH-protein interactions confer added stability.


Funded by NIH SCORE